It is known that, in various cells, chemical stimulation with a bioactive substance or a drug, or physical stimulation with light, electricity, mechanical force, etc, induces a phenomenon, called as “membrane translocation reaction”, of accumulation of certain kinds of intracellular proteins onto a cell membrane. As well known in ones skilled in the art, when a membrane receptor, such as a G protein binding protein on a cell membrane (GPCR: G Protein Coupled Receptor), receives a specific substance (ligand) or a photon, etc. from the exterior, this becomes a trigger, i.e., a stimulus, making the reactions of various materials progress in series within a cell, whereby stimulus information is transmitted one after another within the cell. “Membrane translocation reaction” is a phenomenon as a part of such processes of the stimulus or signal information transmission in a cell, in which certain kinds of proteins having been liberated in cytoplasm or present in cellular organelles before the stimulation move to a cell membrane. Such a membrane translocation reaction in a cell is made observable directly under an optical microscope through labeling fluorescent dye, etc. on proteins or other biological molecules having a membrane translocation activity (producing a membrane translocation reaction), and thus, in the fields of cell biological, medical and pharmacological researches and drug designing, it has been tried to judge whether or not an arbitrary cell produces a membrane translocation reaction in response to an arbitrary material or stimulus under an optical microscope, thereby evaluating whether or not the arbitrary material or stimulus has a physiology activity (especially as an intracellular signal transmitter substance) to the arbitrary cell, or whether or not the arbitrary material or stimulus is effective as a new medicine or a treatment (Drug Discovery).
In the past, in the trial of observation of a membrane translocation reaction, the labeling of a specific protein having a membrane translocation activity in a living cell required a skilled technique, such as microinjection of fluorescently labeled proteins or biological molecules, etc. into individual cells, and also, in this case, the number of cells observable at once was small. However, through staining specific proteins in many cells at once with a fluorescent dye capable of being taken in a living cell and labeled to a specific material or through cultivating at once a large number of cells in which a protein fusing with a fluorescent protein, such as GFP, is expressed through gene introduction technique, it is becoming possible to observe motions of intracellular proteins in many cells by using the fluorescent dye or fluorescent protein as a label. For instance, as described in non-patent document 1, it has been carried out for adhesive cells Hela (cervical cancer cells), etc., to prepare a large quantity of the cells in which GFP-fused protein of protein kinase C (PKC), membrane-translocation-active protein, is made expressed through gene introduction technique, and to observe and judge, under a fluorescence microscope, whether or not a membrane translocation reaction occurs when a membrane translocation signal PMA or other active drug is applied to many cells expressing GFP-fused PKC (It is known that PKC, which has been liberated in cytoplasm before stimulation, binds to the inside of a cell membrane when the cell receives a stimulus of PMA, etc.). According to such an experiment, it becomes possible to observe and evaluate a cellular responsiveness to a certain stimulus for many cells at once, and thus, it is very advantageous for the search of an intracellular signal transmitter substance and the screening of arbitrary substances having a physiological activity.